Subjective response to alcohol and associated craving in heavy drinkers vs. alcohol dependents: an examination of Koob's allostatic model in humans

Abstract

Background: Koob's allostatic model of addiction emphasizes the transition from positive reinforcement to negative reinforcement as dependence develops. This study seeks to extend this well-established neurobiological model to humans by examining subjective response to alcohol (SR) as a biobehavioral marker of alcohol reinforcement. Specifically, this study examines (a) differential SR in heavy drinkers (HDs) vs. alcohol dependent individuals (ADs) and (b) whether HDs and ADs differ in terms of the association between SR and craving.

Methods: Data was culled from two alcohol challenge studies, totalling 91 participants (oversampled on OPRM1 Asp40 carriers). Alcohol was administered intravenously and participants completed standard measures of SR and craving at BrAC's of 0.02, 0.04, and 0.06 g/dl. SR was modeled as a multi-dimensional construct consisting of stimulation, sedation, and tension relief.

Results: ADs reported significantly higher sedation and craving initially and exhibited a blunted response to alcohol along escalating BrACs. ADs exhibited greater initial tension but did not differ from HDs in tension reduction across rising BrACs. Further, alcohol-induced stimulation was associated with alcohol craving to a significantly greater degree in HDs, as compared to ADs.

Conclusions: This study provides initial evidence that HDs and ADs differ in their subjective experience of alcohol and in the association between dimensions of SR and craving for alcohol. Hypotheses derived from the allostatic model were partially supported, such that, while ADs and HDs did not differ on stimulation response, there was a relative dissociation between positive reinforcement and craving in ADs as compared to HDs.

Keywords: Alcohol challenge; Alcoholism; Latent growth modeling; Subjective response to alcohol.

Figure 1

Drinking Status (0 = Heavy Drinking [n=49]; 1 = Alcohol Dependent [n=42]) predicting domains of subjective response to alcohol, as assessed by the BAES Stimulation and Sedation subscales (Stim and Sed respectively), the Tension subscale of the POMS (Tens), and alcohol craving as assessed by the AUQ. For ease of presentation, factor loadings for latent growth parameters, covariances between independent variables, and error terms are not depicted.

Figure 2

Dimensions of subjective response predicting alcohol craving intercept and slope in Heavy Drinkers vs. Alcohol Dependent Individuals. The path from stimulation slope to craving slope was found to differ significantly between alcohol groups (χ² = 3.919, p < 0.05) such that increases in stimulation along rising BrAC were more strongly associated with increased craving for alcohol in heavy drinkers as compared to alcohol dependent individuals. Stim= BAES stimulation subscale, Sed = BAES sedation subscale, Tens = POMS tension subscale, Crave = alcohol craving assessed by the AUQ, Int = latent intercept parameter, Slope = latent slope parameter. For ease of presentation only latent constructs are depicted.